Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

HRID 1043412Notes

Reaction equation

HRID 1043412 reaction equation
[H-].[Na+].[OH:3][C@:4]1([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH:34]=[CH2:35])=[CH:24][CH:23]=2)[CH2:8][N:7]([C:9]([O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])=[O:10])[C@H:6]([C:18]([O:20][CH3:21])=[O:19])[CH2:5]1.[CH3:36]I>CN(C=O)C>[CH3:36][O:3][C@:4]1([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH:34]=[CH2:35])=[CH:26][CH:27]=2)[CH2:8][N:7]([C:9]([O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])=[O:10])[C@H:6]([C:18]([O:20][CH3:21])=[O:19])[CH2:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59266527(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 59266517(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylateYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% in oil) (0.08 g, 1.925 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (0.5 g, 1.069 mmol) and methyl iodide (0.12 mL, 1.925 mmol) at 0° C. in DMF. This was stirred at 0° C. for 3 hrs. The reaction was then quenched with a saturated NH4Cl solution and ether. The ether layer was washed with brine, dried over MgSO4, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (20-40% EtOAc in hexanes) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (160 mg, 31% yield) as a clear oil. LCMS: rt=2.11 min. [M+Na]+=504; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm −0.04-0.13 (m, 9H) 0.95-1.02 (m, 1H) 1.03-1.08 (m, 1H) 2.55 (dd, J=13.12, 8.85 Hz, 1H) 2.76-2.89 (m, 1H) 3.00 (s, 3H) 3.68-3.77 (m, 1H) 3.78 (s, 3H) 3.96-4.09 (m, 1H) 4.20-4.31 (m, 2H) 4.64 (dd, J=8.70, 1.98 Hz, 1H) 5.22 (d, J=11.90 Hz, 1H) 5.72 (d, J=17.40 Hz, 1H) 6.69 (ddd, J=17.40, 10.99, 2.44 Hz, 1H) 7.29 (d, J=7.32 Hz, 1H) 7.32-7.45 (m, 6H) 7.66 (d, J=7.32 Hz, 1H).

Workup

  1. customThe reaction was then quenched with a saturated NH4Cl solution and ether
  2. washThe ether layer was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude material
  7. customThe crude material was purified by flash chromatography on the Biotage (20-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f2788f085a3844d1a387c13897fbe087
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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